tetano
Editor, Senior Moderator
PLoS One. 2014 Jun 13;9(6):e98685. doi: 10.1371/journal.pone.0098685. eCollection 2014.
Protective immunity and safety of a genetically modified influenza virus vaccine.
Barbosa RP1, Salgado AP2, Garcia CC3, Filho BG2, Gon?alves AP2, Lima BH3, Lopes GA3, Rachid MA4, Peixoto AC3, de Oliveira DB5, Ata?de MA6, Zirke CA2, Cotrim TM2, Costa EA2, Almeida GM5, Russo RC3, Gazzinelli RT7, Machado Ade M2.
Author information
Abstract
Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Δ) and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired (RAG -/-) immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Δ infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens.
PMID:
24927156
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24927156
Protective immunity and safety of a genetically modified influenza virus vaccine.
Barbosa RP1, Salgado AP2, Garcia CC3, Filho BG2, Gon?alves AP2, Lima BH3, Lopes GA3, Rachid MA4, Peixoto AC3, de Oliveira DB5, Ata?de MA6, Zirke CA2, Cotrim TM2, Costa EA2, Almeida GM5, Russo RC3, Gazzinelli RT7, Machado Ade M2.
Author information
Abstract
Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Δ) and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired (RAG -/-) immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Δ infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens.
PMID:
24927156
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24927156